Javier Calleja's men will hardly view Atletico as ideal opponents as they look to end a winless run of five games in La Liga and create some badly-needed momentum.
Following an excellent first campaign under Calleja during the 2017-18 season, during which Villarreal finished fifth, the club has markedly struggled for consistency, stumbling to 14th position last term and currently languishing in a similar position after 14 games this time around.
There is plenty of talent in this team and a potential to cause opponents serious damage, as seen through a rampant 5-1 win over Real Betis in September, with striker Karl Toko Ekambi pulling the visitors all over the pitch with his electric movement.
But as Villarreal prepare to face Atletico, they will know that this ability has to be coupled with the perfect mindset over 90 minutes if they are to arrest this current slump in results.
Following a summer of such fundamental change, at a club that for so long seemed to stay relatively the same, you can perhaps understand why there are some teething problems for this new-look Atletico side.
The club spent almost £220m on transfers over the summer, with eight players coming in, while members of the old guard such as Juanfran, Diego Godin, Antoine Griezmann and Filipe Luis moved elsewhere.
Normally a team guaranteed to sit in La Liga's top three, Atletico currently find themselves off the pace in sixth following a string of performances that have been evocative of a team whose moving parts are not perfectly in sync like they were during the golden days between 2013 and 2015.
Perhaps the most telling fact of this season is that Atletico, despite signing the superb Joao Felix, have only mustered 16 goals from 14 La Liga games - the lowest of any of the top 14 teams in the division.
As they travel east to face Villarreal, Atletico will know that failure to improve that record sooner rather than later could leave them under serious threat of missing out on the Champions League next season.
Recent Villarreal form: WLDLLL
Recent Atletico Madrid form: DLWDLL
A huge miss for Villarreal will be Cazorla, who has a sprained ankle, along with former Liverpool defender Alberto Moreno, with the latter suffering a thigh problem.
Another important player in the form of Angel Correa will also miss out after picking up an accumulation of yellow cards.
Villarreal possible starting lineup:
Asenjo; Mario, Albiol, Torres, Quintilla; Morlanes; Trigueros, Anguissa, Chukwueze, Moreno; Toko Ekambi
Atletico Madrid possible starting lineup:
Oblak; Trippier, Felipe, Hermoso, Lodi; Herrera, Thomas, Lemar, Koke; Morata, Felix
We say: Villarreal 1-2 Atletico Madrid
Neither team enters this game in particularly good form, but Villarreal will be especially concerned following three straight defeats, while Atletico still have more than enough quality to bring this game under their control.